Have government scientists solved the artificial hips corrosion problem?

Have government scientists solved the artificial hips corrosion problem? (TMG Pulse – Released on August 8, 2019 | Written by Nancy Crotti of Medical Design and Outsourcing

Argonne National Laboratory researchers tested metal alloys that ortho device companies have used in artificial hips for decades. 

Materials scientists at the U.S. Department of Energy’s Argonne National Laboratory usually test metal alloys for their ability to contain nuclear waste for millions of years. A couple of years ago, two of them decided to apply their expertise to evaluate metal alloys used in artificial hips.

Now they’re seeking to patent a method that they say does a better job than standard ASTM tests of showing how well hip implants will endure conditions in the human body before corrosion sets in.

Their work could matter because the orthopedic device industry has been facing a crisis over materials: Corrosion of the metals used in artificial hips have been linked to metallosis, or metal poisoning. Symptoms include bone and tissue death, implant failure and severe pain. Implant makers have reached billions of dollars in legal settlements and researchers continue to study and test alternatives.

Argonne’s Vineeth Kumar Gattu began testing metal alloys used in artificial hips after attending a conference on corrosion in 2017. Gattu found that conventional tests are too short and lack the rigor needed to gauge how materials truly perform in the body, partly because they don’t represent the environmental conditions within the body. They may not consider the range of conditions that can occur within the body and corresponding changes in the material surface, he said.

Materials scientists test for oxidation, or corrosion, using different techniques, such as by measuring a material’s electrochemical responses to its environment. In one type of electrochemical test, scientists apply voltages to the material and measure the resulting electrical currents. The current shows how quickly the material is oxidizing. These tests tend to focus on the short-term response at one voltage level, representing just one electrochemical scenario, Gattu said.

“Every biological environment has a redox (reduction-oxidation) strength that changes with physical activity,” he said. “Oxygen levels in the blood are different when you are walking, running, or resting. The oxygen saturation levels determine the redox strength and could drive the corrosion rates higher than those observed in the standard tests.”

Gattu and fellow Argonne scientist William Ebert said they applied many voltage levels to hip implant material, sometimes for several days — much longer than standard tests. They also said that the implant material made of cobalt, chromium and molybdenum corroded at high voltages, whereas the other alloy material made of titanium, aluminum, and vanadium remained stable under the same conditions.

Johnson & Johnson’s DePuy Synthes division declined comment on the Argonne research. Other major manufacturers of artificial hips — Zimmer Biomet, Stryker, Smith & Nephew — did not respond to requests for comment.

The metal-on-metal issue

Ortho device companies have been wrestling with major challenges involving materials since the high-profile August 2010 recall of DePuy Orthopaedics’ ASR XL acetabular and ASR hip resurfacing systems. Parent company Johnson & Johnson pulled the implants after receiving reports that a higher-than-normal number of patients required surgeries to correct or remove defective implants. Other device makers have found themselves pulled into the controversy since 2010.

Reports have warned of hundreds of thousands of patients potentially exposed to toxic compounds from the implants, putting them at risk of developing cancer, cardiomyopathy, muscle and bone destruction and changes to their DNA.

Metal-on-metal hips are no longer sold in the U.S., but many patients still have the devices implanted. Interim results from postmarket studies show significantly higher blood levels of metal ions (cobalt and chromium) in patients with metal-on-metal hip implants compared to those without metal implants. However, some patients with higher blood levels had no complications while others with low blood levels reported severe symptoms.

The FDA has said other factors such as device design or surgical placement may have contributed to greater wear-down of the devices and elevated metal ion levels. Hip implants may be affected by infection, fracture, or a combination of normal tribological (related to the synergism between wear and corrosion) and biological processes, such as loosening and wear. About 58% of patients may expect a hip implant to last 25 years, according to a recent study published in The Lancet.

The FDA is working with standards development organizations, such as the American Society for Testing and Materials (ASTM), to develop new standards to improve how metal-on-metal hips are evaluated and identify additional testing protocols for new metal-on-metal devices that are submitted to the FDA for review. The agency will also hold an advisory committee meeting this fall to discuss metal implants and the potential risk for certain patients to have exaggerated immune and inflammatory reactions to the metals in medical devices.

Research continues

The average lifespan of an implanted artificial hip is about 10 to 15 years, according to recent orthopedics research, although some fail after six months while others last for 30 years. One limitation of the implants’ success is the synergistic interaction of wear and corrosion, or tribocorrosion, at the implant interfaces, according to Mathew T. Mathew, associate professor of biomedical science at the University of Illinois at Chicago and a longtime metal alloy researcher. He and colleague Ernesto Indacochea, professor emeritus of civil and materials engineering, are collaborating with Gattu and Ebert.

Mathew and Indacochea are studying the properties of load-bearing and hardness in alloys of cobalt-chromium and molybdenum. They believe one reason for patients’ bodies to react differently to metal implants may be the polarization of cells within each individual’s body, which can cause chemical corrosion in a micro- or nano-area.

“That leads to severe corrosion,” Mathew said. “We are working on predicting the mechanisms of accelerated corrosion due to the influence of mechanical and biochemical environments. Right now, there is no good/optimized test model or implant simulators to investigate such complex processes.”

The University of Illinois teams are also trying to recreate what Indacochea called “the real environment that you have in the body” and performing corrosion tests based on fluctuations in biochemistry, such as pH levels, which change with physical activity.

Another possible corrosion suspect: the pro-inflammatory cytokine Interleukin-17A (IL-17). A 2017 study at hospitals in England and Switzerland found that 10% of 152 end-stage osteoarthritis patients who underwent hip or knee arthroplasty had elevated levels of the IL-17 in the friction-reducing synovial fluid around their affected joints. But such biochemical changes are highly unpredictable and cannot be measured during activity. That’s why it’s important to develop artificial hips that can withstand a wide variety of environments, Gattu said.

It’s complicated

Robin Pourzal is an assistant professor at Rush University Medical Center’s Department of Orthopedic Surgery in Chicago, which has a long-standing orthopedic implant retrieval program. With their permission, Rush collects explanted artificial hips from living and deceased donors for testing purposes. An engineer and a materials scientist, Pourzal has published several papers on the topic and is collaborating with researchers from The Advanced Photon Source at Argonne on the nature of wear and corrosion products within biological tissue around hip replacements.

“We want to see what was caused by wear, what was caused by corrosion, and what was the tissue response to wear and corrosion debris,” Pourzal said. “The truth is, it’s complicated… We want to blame something for certain failures. But there’s a lot going into this — the implant itself, its material and design, the manufacturer, the surgeon, and the patient. Some patients react differently to foreign debris than other patients.”

Vilupanur Ravi chairs the chemical and materials engineering department at California State Polytechnic University, Pomona (Cal Poly Pomona). Ravi and his students have been developing and testing metallic alloys for bio-corrosion for more than 15 years. They have subjected the alloys to different types of electrochemical tests in a variety of solutions relevant to human body environments. They have also explored the response of the materials to different voltages, exposure times and pH conditions.

Ravi has developed a collaboration with Cal Poly Pomona biology professor Steve Alas to examine the response of macrophages to the metals. The team has also been investigating biofilm formation on different alloys in order to analyze how different microbes may colonize the implant after surgery.

The Cal Poly Pomona team has had good results from adding boron to titanium and titanium alloys. Boron is a non-toxic element that in trace amounts can aid in bone maintenance and growth. None of the boron-containing alloys failed the ASTM F2129, the standard corrosion test for small implants, according to Ravi. In addition, the boron-containing alloys elicited a lower level of inflammatory response as measured by lower levels of Interleukin-1β (IL-1β) being secreted. IL-1β is one of the inflammatory cytokines that could provide insights into long-term implant compatibility.

“We have found out that some of the boron-containing alloys had outstanding corrosion behavior and excellent mechanical properties,” he said.

The Argonne scientists have not published their work while awaiting the patent process, so there’s not much for others to go on by way of comparison. Ravi said that, judging from an Argonne press release and video, the national lab’s scientists are on the same track as his team.

Gattu expects the Argonne team’s patent to be approved in 2020. The team is also working with a couple of implant makers, whom Gattu declined to identify.

“Argonne is claiming they have found a new method to predict long-term implant performance and while that is great, I would advocate a cautious approach” Ravi said. “The thing is that, in the human body, there are a lot of events going on that involve live cells as well. So when you do an in vitro test… it’s only one piece of the puzzle.”

Pourzal agreed. “Unfortunately, the only true environment that puts the implant really to the test is the human body,” he said. “Establishing better, more realistic preclinical testing methods is key.”

Original Article: (https://www.medicaldesignandoutsourcing.com/have-government-scientists-solved-the-artificial-hips-corrosion-problem/)